RT Journal Article
SR Electronic
T1 Bone morphogenetic protein and growth differentiation factor cytokine families and their protein antagonists
JF Biochemical Journal
JO Biochem J
FD Portland Press Ltd
SP 1
OP 12
DO 10.1042/BJ20100305
VO 429
IS 1
A1 Rider, Christopher C.
A1 Mulloy, Barbara
YR 2010
UL http://www.biochemj.org/content/429/1/1.abstract
AB The BMPs (bone morphogenetic proteins) and the GDFs (growth and differentiation factors) together form a single family of cystine-knot cytokines, sharing the characteristic fold of the TGFβ (transforming growth factor-β) superfamily. Besides the ability to induce bone formation, which gave the BMPs their name, the BMP/GDFs display morphogenetic activities in the development of a wide range of tissues. BMP/GDF homo- and hetero-dimers interact with combinations of type I and type II receptor dimers to produce multiple possible signalling complexes, leading to the activation of one of two competing sets of SMAD transcription factors. BMP/GDFs have highly specific and localized functions. These are regulated in a number of ways, including the developmental restriction of BMP/GDF expression and through the secretion of several specific BMP antagonist proteins that bind with high affinity to the cytokines. Curiously, a number of these antagonists are also members of the TGF-β superfamily. Finally a number of both the BMP/GDFs and their antagonists interact with the heparan sulphate side chains of cell-surface and extracellular-matrix proteoglycans. Abbreviations: ActR, activin A receptor; ALK, activin receptor-like kinase; BMP, bone morphogenetic protein; BMPR, BMP receptor; Dan, differential screening-selected gene aberrative in neuroblastoma; CAN, Cerberus and Dan; Dpp, decapentaplegic; EMT, endothelial-to-mesodermal transition; FSTL, follistatin-like; GDF, growth and differentiation factor; HS, heparan sulphate; LRP, low-density-lipoprotein-receptor-related protein; PRDC, protein related to Dan and Cerberus; R-SMAD, regulatory SMAD; TGF-β, transforming growth factor-β; TSG, twisted gastrulation; USAG-1, uterine sensitivity-associated gene-1